Acupuncture is emerging as an important modality in complementary medicine. Its mechanism of action remains unclear. Given the modulatory action of acupuncture on many mental and physiological functions, we hypothesize that its effects are mediated via the limbic system and its closely related structures in the cortex and brainstem, a widely connected network that is involved in the regulation of mood, behavior and functions of multiple physiological systems. We shall employ the powerful and noninvasive fMRI technique (BOLD) to monitor the central effects of manual acupuncture at commonly used acupuncture points on normal human subjects. An initial study using LI 4 on the hand demonstrated quantifiable and regionally specific signal changes that indicate modulatory effects on limbic, paralimbic and subcortical gray structures. The effects were not observed in control tactile stimulation and were distinct from response to pain (Hui et al, 00, 01). We propose a new study that will encompass the whole brain in order to demonstrate that limbic related regions in the cortex and brainstem will respond in a similar manner. We shall compare the central effects of acupuncture points of different meridians (specific routes of acupuncture points) and of different segmental innervations to determine the regional specificity of limbic and somatosensory areas. Furthermore, we shall use a special technique that targets the brainstem to examine effects on the descending antinociceptive pathway. The studies are aimed at the beginning of imaging neuroscience-based investigation of the central effects of acupuncture and will provide a scientific basis for the understanding of the therapeutic potentials of this ancient healing technique.